Chronic copper exposure elicit neurotoxic responses in rat brain: Assessment of 8-hydroxy-2-deoxyguanosine activity, oxidative stress and neurobehavioral parameters

Abstract

Copper (Cu), one of the essential transition metal acts as a prosthetic group for variety of proteins and metalloenzymes. However, it may be hazardous when administered in excess. Copper induced memory impairment and progression of neurodegenerative diseases have not yet been fully elucidated. The aim of the present study was to investigate the effect of exposure to copper sulphate (10mg/kg and 20mg/kg body weight, daily for 16 weeks) on brain copper concentration, few biochemical parameters indicative of oxidative stress and on different neurobehavioral functions in male Sprague Dawley rats. Copper-administered animals showed significant increase in brain copper concentration and a depleted Ceruloplasmin level. Different neurobehavioral studies revealed impaired memory and motor coordination in copper exposed rat. Spontaneous locomotors activity and depression symptoms were also noted in copper intoxicated rats. 8-hydroxy-2' -deoxyguanosine (8-OHdG) level, one of the predominant forms of free radical-induced oxidative lesions, and has been widely used as a biomarker for oxidative stress, increased in copper treated group. Copper induced oxidative stress in the brain was also evident from the increased lipid per oxidation (LPO) and nitrite level, depletion of reduced glutathione (GSH), and reduced activities of the antioxidant enzymes such as superoxide dismutase (SOD), and catalase. The present study thus suggests a significant correlation between copper induced oxidative stress and changes in neurobehavioral function in rats. The changes were more pronounced in animals exposed to a higher dose of copper (20mg/kg) than the lower dose.

Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

“…Copper (Cu) can enter into cells though the copper transporter 1 ( 27 , 28 ). Excessive Cu accumulation in multiple organs (e.g., brain, kidney, heart, liver, and reproductive organs) due to both acute and chronic uptake causes potential toxic effects, including nephrotoxicity, hepatotoxicity, neurotoxicity and reproductive toxicity ( 4 , 10 , 11 , 29 – 31 ). In line with the previous studies ( 4 ), our current study showed that CuSO 4 exposure at the dose of 200 mg/kg/day for 28 days caused marked nephrotoxicity in mice, observed through the upregulation of serum BUN and CRE levels, as well as histopathological damage ( Figures 2 , 3 ).…”

Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

“…There have been reports that mention the possible toxic effects of heavy metals, such as As, Cd, Pb, Hg, and Cu in CSVD associated disorders such as stroke, ischemia, dementia, amyloid angiopathy, etc. [39][40][41].…”

Advances in the mechanism of high copper diets in restraining pigs growth

“…Similarly, as copper exposure induces oxidative stress, long‐term and excessive intake of copper may reduce the activities of various digestive enzymes in the intestine (Chen et al, ), decrease the rate of digestion, prolong chyme transit time in the intestine, enhance satiety and thus inhibit food intake (Gotteland, Araya, Pizarro, & Olivares, ; Sohal & Allen, ) as illustrated in Figure . Moreover, the antibacterial properties of high copper can change the microbial polymorphism of the pig's intestine (Di Giancamillo et al, ; Kumar et al, ; Papaioannou et al, ; Shurson et al, ; Zhang, Wu, et al, ), thereby influencing the composition of intestinal microbes. The change in the composition of intestinal microbial content may affect the utilization of cellulose in the gut and the regeneration of liver tissue, hence affecting the ability of the liver to secrete bile acids.…”

“…High copper supplementation in pig production has gained popularity and increased usage due to the ban on antibiotics use in some parts of the world (Adams et al, 2019;Che et al, 2018). Several studies have reported that high copper supplementation may not only regulate the activities of various enzymes such as digestive enzymes and antioxidant enzymes in pigs, but also may regulate the growth signalling pathways, feeding and fasting signalling pathways, and hence improve protein deposition and promote bone formation (Chen, Mayer, Weston, Bock, & Jumars, 2002;Kumar, Sathua, & Flora, 2019;Kumar, Kalita, Bora, & Misra, 2016a, 2016bKumar, Kalita, Misra, & Bora, 2015). In addition, studies have shown that the rational use of high copper diets may improve intestinal structure and function (Mei, Yu, Ju, Zhu, & Chen, 2009;Yang et al, 2011).…”